Asthma appears to be a disease that is driven by a predominantly Th2 immune response to environmental antigens. CD4 T cell effector responses are, however, extensively regulated under normal circumstances with Th2 responses being modulated by Th1 CD4 T cells, as well as by other mechanisms. Costimulatory molecules play a critical role in the activation and differentiation of CD4 T cells. Recently, the costimulator ICOS has been discovered to be expressed on activated T cells, where it seems to play a critical role in the differentiation of CD4 T cells to effector cells producing a number of critical cytokines such as IL4 and IL13. In this proposal, we will utilize ICOS deficient mice that were recently generated in the laboratory of the PI to elucidate the cellular and molecular mechanisms whereby ICOS regulates Th2 cytokine gene expression, and the role that ICOS plays in regulating the immune response and pathology, in ovalbumin and HDI mouse models of asthma.